Q2 2024 Voyager Therapeutics Inc Earnings Call

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Operator: Good afternoon, and welcome to the Voyager Therapeutics second quarter 2024 financial results conference call. This time, all participants are in listen-only mode. There will be a question and answer session at the end of this call. Please note that today's call is being recorded. Replay of today's call will be available on the investor section of the company website approximately two hours after the completion of this call. I would now like to turn the call over to Trista Morrison, Chief Corporate Affairs Officer at Voyager.

Unknown Executive: Good afternoon and welcome to the Voyager Therapeutics second quarter, 2024 financial results conference call. This time, all participants are in listen-only mode. There will be a question and answer session at the end of this call.

Speaker Change: Good afternoon, and welcome to the Voyager Therapeutics second quarter 'twenty 'twenty four financial results conference call.

Speaker Change: At this time, all participants are in listen only mode.

Speaker Change: There will be a question and answer session at the end of this call.

Unknown Executive: Please note that today's call is being recorded. Replay of today's call will be available on the investor's section of the company website approximately two hours after completion of this call.

Speaker Change: Please note that today's call is being recorded.

Speaker Change: Play of today's call will be available on the investors section of the company website approximately two hours after completion of this call.

Trista Morrison: I would now like to turn the call over to Trista Morrison, Chief Corporate Affairs Officer at Voyager. Thank you and good afternoon. We issued our second quarter 2024 financial results press release this afternoon. The press release in 10-Q are available on our website.

Trushar Morrison: I would now like to turn the call over to trust her Morrison Chief Corporate Affairs officer at Voyager.

Trista Morrison: Thank you, and good afternoon. We issued our second quarter 2024 financial results press release this afternoon. The press release and the 10Q are available on our website. Joining me on today's call are Dr. Al Sandrock, our Chief Executive Officer; Dr. Toby Ferguson, our Chief Medical Officer; and Dr. Nathan Jorgensen, our Chief Financial Officer. We will also be joined for the Q&A portion of the call by Dr. Todd Carter, our Chief Scientific Officer.

Trisha Morrison: Thank you and good afternoon, we issued our second quarter 2024 financial results press release this afternoon.

Speaker Change: Press release, and 10-Q are available on our website joining me on today's call are Dr. Al Sandrock, Our Chief Executive Officer, Dr. Toby Ferguson, our Chief Medical Officer, and Dr. Nathan Jorgensen, our Chief Financial Officer.

Trista Morrison: Joining me on today's call are Dr. Alfandrak, our Chief Executive Officer, Dr. Toby Ferguson, our Chief Medical Officer, and Dr. Nathan Jorgensen, our Chief Financial Officer. We will also be joined for the Q&A portion of the call by Dr. Todd Carter, our Chief Scientific Officer.

Speaker Change: We will also be joined for the Q&A portion of the call by Dr. Tom Carter, our Chief Scientific Officer.

Trista Morrison: Before we get started, I'd like to remind everyone that during this call, Voyager representatives may make forward-looking statements, as noted in slide two of today's call. These statements are based on our current expectations and beliefs. They are subject to risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings, which are available on our website, for additional details. And now, I will turn the call over to Al.

Trista Morrison: Before we get started, I'd like to remind everyone that during this call, Voyager representatives may make forward-looking statements, as noted in slide two of today's deck. These statements are based on our current expectations and beliefs. They are subject to risks and uncertainties, and actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings, which are available on our website for additional detail.

Speaker Change: Before we get started I'd like to remind everyone that during this call wager Representatives may make forward looking statements as noted in slide two of today's deck. These statements are based on our current expectations and beliefs. They are subject to risks and uncertainties and our actual results may differ materially I encourage you to consult the risk factors.

Al Sandrock: Discussed in our SEC filings, which are available on our website for additional detail and now I will turn the call over to al.

Alfandrak: And now I will turn the call over to Owl. Good afternoon, everyone, and thank you for joining us. Please turn to slide three. At Voyager, we are leveraging the power of human genetics to discover and develop transformative medicines that address the root cause of neurological diseases. We have made tremendous progress toward this call in 2024, including the achievement of several important milestones in the second quarter. In May, we dose the first healthy volunteers in the phase 1A single-offending dose trial of Voy7523, formally called Voy101, our anti-tau antibody designed to inhibit the spread of pathological tau in Alzheimer's disease.

Alfred Sandrock: Good afternoon, everyone, and thank you for joining us. Please turn to slide three.

Al Sandrock: Good afternoon, everyone and thank you for joining us.

Al Sandrock: Please turn to slide three.

Alfred Sandrock: At Voyager, we are leveraging the power of human genetics to discover and develop transformative medicine that addresses the root cause of neurological diseases. We have made tremendous progress toward this goal in 2024, including the achievement of several important milestones in the second quarter. In May, we dosed the first healthy volunteers in the Phase 1a single ascending dose trial of VY-7523, formerly called VY-Tau-01, our anti-tau antibody designed to inhibit the spread of pathological tau in Alzheimer's. Enrollment in this study is on track, and we expect to report top-line safety and pharmacokinetic data in the first half of next year.

Al Sandrock: At Voyager, we are leveraging the power of human genetics to discover and develop transformative medicines that address the root cause of neurological diseases.

Al Sandrock: We have made tremendous progress toward this goal in 2024, including the achievement of several important milestones in the second quarter.

Al Sandrock: In May we dose the first healthy volunteers in the phase one single ascending dose trial.

Speaker Change: Why $75 23, formerly called <unk> zero, one our anti Tau antibody designed to inhibit the spread of pathological Tau and Alzheimers disease.

Alfandrak: Enrollment in this study is on track, and we expect to report top line safety and pharmacokinetic data in the first half of next year. Toby will provide additional detail on our tau directed programs in just a bit. We continue to advance our robust pipeline of wholly owned and partnered CNS gene therapy programs, and we continue to expect IND filings for three of these programs next year. In the second quarter, we completed a pre-IND meeting with the FDA and initiated GLP toxicology studies for VY-9323, our wholly owned SOD-1 silencing gene therapy program for SOD-1 ALS. Also this quarter, we selected a development candidate in our GBA-1 gene therapy program partnered with Neracron, triggering a $3 million milestone payment to Voyager.

Speaker Change: Enrollment in this study is on track and we expect to report top line safety and pharmacokinetic data in the first half of next year.

Alfred Sandrock: Toby will provide additional detail on our TAO-directed programs in just a bit. Meanwhile, we continue to advance our robust pipeline of wholly owned and partnered CNS gene therapy programs, and we continue to expect IND filings for three of these programs next year. In the second quarter, we completed a pre-IND meeting with FDA and initiated GLP toxicology studies for VY9323, our wholly owned SOD1 silencing gene therapy program for SOD1 ALS. Also this quarter, we selected a development candidate in our GBA1 gene therapy program partnered with Neurocrin, triggering a $3 million milestone payment to Voyager.

Speaker Change: Toby will provide additional detail on our Tau directed programs in just a bit.

Toby Ferguson: We continue to advance our robust pipeline of wholly owned and partnered CNS gene therapy programs and we continue to expect IND filings for three of these programs next year in the second quarter, we completed a pre IND meeting with FDA and initiated GOP toxicology.

Toby Ferguson: Studies for the Y $93 23, our wholly owned <unk> silencing gene therapy program for <unk> AOS.

Toby Ferguson: Also this quarter, we selected a development candidate in our GBA, one gene therapy program partnered with Neurocrine, triggering a $3 million milestone payment to Voyager.

Alfandrak: This follows the development candidate selection that occurred in the first quarter on our Neurclan Partner Gene Therapy program for Friedrich's Ataxia.

Toby Ferguson: This followed the development candidate selection that occurred in the first quarter on our Neurocrine partnered gene therapy program for free drive say tax here.

Alfandrak: In June, we appointed Nathan Jorgensen as Chief Financial Officer of Voyager. Nate brings a highly differentiated breadth of experience spanning investment banking, healthcare investing, operational leadership roles in biotech, and a PhD in neuroscience. I'm already seeing the benefits of his strategic financial expertise. Our team presented an impressive body of data at ASGCT 2024 in May, including data on our second-generation tracer capsis, their translatability as evidenced by cross-species and receptor data, and activity against therapeutic targets in Alzheimer's disease and ALS. These posters and presentations are available on our website, in case you miss them. Finally, we ended the second quarter with a strong cash position of approximately $371 million, which, based on our current operating plans, we expect to provide runway through multiple clinical data readouts into 2027.

Nathan Jorgensen: In June we appointed Nathan you, Oregon soon as Chief Financial Officer of Voyager.

Nathan Jorgensen: <unk> brings a highly differentiated breadth of experience spanning investment banking healthcare investing operate operational leadership roles in biotech and a ph D in neuroscience.

Speaker Change: I'm already seeing the benefits of his strategic financial expertise.

Speaker Change: Our team presented an impressive body of data at <unk> 2024 and May <unk>.

Speaker Change: <unk> data on our second generation tracer capsid, theyre translate ability as evidenced by cross species and receptor data and activity against therapeutic targets in Alzheimer's disease and AOS.

Speaker Change: These posters and presentations are available on our website in case you missed them.

Speaker Change: Finally, we ended the second quarter with a strong cash position the approximately $371 million, which based on our current operating plans, we expect to provide runway through multiple clinical data readouts into 2027.

Alfandrak: The progress we made in the second quarter feeds into our four pillars of value, which are outlined on slide four. First is our pipeline of four wholly owned and 13 partnered programs. As I mentioned, our anti-tow antibody, VY7523, is in a single ascending dose trial, and we have three gene therapies tracking to INDs next year. This sets up for multiple potential data readouts in 2025 and 2026. Second is our industry-leading tracer platform for the discovery of novel AAV capsids to enable CNS gene therapy. As the data we presented at ASGCT reinforced, our second-generation capsids have demonstrated robust transduction of key CNS cell types and significant liver detargeting following a single IV dose.

Speaker Change: The progress we made in the second quarter feeds into our four pillars of value, which are outlined on slide four.

Speaker Change: First is our pipeline of four wholly owned and 13 partnered programs.

Speaker Change: As I mentioned, our anti Tau antibody <unk> $75 23 is in a single ascending dose trial and we have three gene therapies tracking to IND next year.

Speaker Change: This sets up for multiple potential data readouts in 2025 and 2026.

Speaker Change: Sure.

Speaker Change: Second is our industry, leading tracer platform for the discovery of novel AAV capsid to enable CNS gene therapy.

Speaker Change: As the data we presented as GCT reinforced our second generation capsid have demonstrated robust transduction of key CNS cell types and significant liver targeting following a single IV dose.

Alfandrak: These capsis have enabled the selection of multiple development candidates in our wholly owned and partnered gene therapy programs. Third, we have blue chip partnerships with some of the world's experts in neurology and gene therapy, including Neurocran, Novartis, and Alexion. In total, our partnered programs could generate up to $8.2 billion in longer-term milestone payments. Finally, we continue to explore the potential to leverage receptors we have identified to shuttle non-viral genetic medicines into the brain. Ultimately, we aim to expand from gene therapy and antibodies into other modalities of neurogenetic medicine, broadening our impact.

Speaker Change: These captives have enabled a selection of multiple development candidates in our wholly owned and partnered gene therapy programs.

Speaker Change: Third we have blue chip partnerships with some of the world's experts in neurology and gene therapy, including Neurocrine Novartis and <unk>.

Speaker Change: In total our partner programs could generate up to $8 $2 billion and longer term milestone payments.

Speaker Change: Finally, we continue to explore the potential to leverage receptors, we have identified to shuttle non viral genetic medicines into the brain.

Speaker Change: Ultimately, we aim to expand from gene therapy and antibodies into other modalities of narrow genetic medicine broadening our impact.

Toby Ferguson: With that, I'll turn the call over to Toby to share his conviction on our TAO and gene therapy program. Thanks, Al, and good afternoon. Please turn to slide 5. This slide summarized the four wholly owned programs and 13 partner programs that Al mentioned earlier. We won't discuss all of these programs today, but I do want to spend a few minutes on some of our more advanced programs. First, the presence of tau pathology in the brain is a defining feature of the disease. Second, a wealth of evidence demonstrates that the accumulation and spread of tau pathology to the brain closely correlates with clinical decline in Alzheimer's disease.

Toby Ferguson: With that I'll turn the call over to Toby to share his conviction on our Tau in gene therapy programs.

Toby Ferguson: Thanks, Al, and good afternoon. Please turn to slide five.

Toby Ferguson: Thanks Al and good afternoon, Please turn to slide five this slide summarize the four wholly owned programs and 13 partner programs that Al mentioned earlier, we won't discuss all of these programs today, but I do want to spend a few minutes on some of our more advanced programs.

Toby Ferguson: This slide summarizes the four wholly-owned programs and 13 partner programs that Al mentioned earlier. Turning to slide 6, I want to focus for a moment on our two wholly owned programs that target, Importantly, recent third-party clinical data generated using an intrathecally-administered tau-directed antisense oligonucleotide. Anti-Tau Antibody Designed to Inhibit the Cell-to-Cell Spread of Pathological Tau in the Brain, in an in vivo model of human tau spread, the mirroring surrogate of VY7525. We are also advancing a child silencing gene therapy.

Speaker Change: Turning to slide six I want to focus for a moment or two wholly owned programs that target Tau.

Speaker Change: There are a few reasons, we believe that Tau is critically important for the treatment of all servers disease first the presence of Tau pathology in the brain is a defining feature of the disease.

Speaker Change: Second a wealth of evidence demonstrates that the accumulation and spread of Tau pathology to the blade closely correlates with clinical decline Alzheimers disease.

Toby Ferguson: Third, the spread of tau pathology can be readily visualized in vivo with tau PET imaging, enabling the enrollment of appropriate individuals in clinical studies and providing a quantitative biological readout that is likely to predict clinical outcomes. Importantly, recent third-party clinical data generated using an interethically administered tau-directed anti-sense oligonucleotide showed that reducing tau expression was associated with favorable trends on clinical outcomes.

Speaker Change: Third the spread of Tau pathology can be readily visualized in vivo with Tau pet imaging.

Speaker Change: Enrollment of appropriate individuals in clinical studies and provided a quantitative biological readout that is likely to predict clinical outcomes.

Speaker Change: Importantly, recent third party clinical data generated using an interest likely administered tau directed antisense oligonucleotides.

Speaker Change: Showed that reducing tau expression was associated with a favorable trends or clinical outcomes.

Toby Ferguson: At Voyager, we are advancing two complementary approaches to reduce tau pathology in Alzheimer's disease. VY7523, formerly called VY-TOW-01, is an anti-tau antibody designed to inhibit the self-to-self spread of pathological tau in the brain. In contrast to third-party anti-tap antibody approaches, the target of the end-term-minus of tau has been unsuccessful in the clinic, VY7523 targets a C-terminal epitope of pathological tau. In an in vivo model of human tau spread, the mirroring surrogate of VY7523 inhibits tau spread by approximately 70%, while end-term-minus directed antibodies that were ineffective in the clinic were also ineffective in the model. This quarter, we dose the first participants in the Phase 1A single ascending dose trial of VY7523 in healthy volunteers.

Voyager: At Voyager, we are advancing two complementary approaches to reduce tau pathology in Alzheimer's disease.

Speaker Change: B why $75 23, formerly called <unk>, one is an <unk> antibody designed to inhibit the cell to cell spread of pathological tau in the brain.

Speaker Change: Contrast, third party anti Tau antibody approaches with targeted the end terminals hotel and have been unsuccessful at clinic Py 70, 523 targets a few terminal epitope of pathological town.

Speaker Change: And in in vivo model of human health spread the murine surrogate of D. Y 70, 523 inhibits how spread by approximately 70% while internally directed antibodies that were ineffective for the clinic. We're also ineffective in the model.

Speaker Change: This quarter, we dosed the first participants in the phase one single ascending dose trial of <unk> $75 43 in healthy volunteers. This randomized double blind placebo controlled trial is designed to evaluate the safety and pharmacokinetics of <unk>.

Toby Ferguson: This randomized double-blind placebo-metral trial is designed to evaluate the safety and pharmacokinetics of VY7523 that are approximately 48 participants across multiple cohorts. Enrollment in this trial is on track, and we expect to report top-line data in the first half of next year. We then plan to conduct a multiple ascending dose study in participants with early Alzheimer's disease. We expect to initiate this trial next year and generate tau initial tau-pat image data in the second half of 2026. That is the potential to show slowing of tau spread.

Speaker Change: Why 70 523.

Speaker Change: <unk> 48 participants across multiple cohorts.

Speaker Change: Enrollment in this trial is on track and we expect to report topline data in the first half of next year.

Speaker Change: We then plan to conduct a multiple ascending dose study in.

Speaker Change: In participants with early Alzheimer's disease.

Speaker Change: We expect to initiate this trial next year.

Speaker Change: And generate initial top image data in the second half of 2026 has the potential to show slowing of Tau spread.

Toby Ferguson: Completing this antibody-based approach, we are also advancing a tau-solocene gene therapy program. This program deploys a tau-SART-targeted siRNA packaged in IV administered tracer capsid. Using this approach, we have demonstrated robust reductions in human tau mRNA and protein across the brain following a single IV administration in my expressing human tau. We believe this program has the potential to provide a transformative, single-treatment of Alzheimer's disease, and we anticipate filing in 90 in 2026.

Speaker Change: Complementing this antibody based approach we are also advancing age households in gene therapy program.

Toby Ferguson: This program deploys a Tau-SARC-targeted siRNA packaged in an IV-administered tracer catalyzer. Using this approach, we've demonstrated robust reductions in human tau mRNA and protein across the brain upon a single IV administration in mice expressing the Neurocrine Partner at GBA. We expect to file an IND for VY 9323 in the middle of next year and initiate clinical trials in SODOM and ALS patients after the IND is approved, consistent with our strategy to generate rapid proof of biology in our clinical program. We aim to assess validated biomarkers of target engagement and disease progression in this trial. With that, I'll turn the call over to

Speaker Change: This program deploys that house are targeted at the IR day packaged with IV administered tracer capsid user.

Speaker Change: Using this approach we've demonstrated robust reductions in human Tau mrna and protein across the brain probably by a single IV administration in mice expressing human talent.

Speaker Change: We believe this program has the potential to provide a transformative single street with Alzheimers disease.

Speaker Change: Anticipate filing an IND in 2026.

Toby Ferguson: Turning to slide steps. In addition to our program's targeting tile, we're also advancing three gene therapy programs for which we expect eye-and-e-file ones next year. They include. As a reminder, we have demonstrated that a single IV administration of VY 93-23, at a clinically relevant dose of three E-13 vector genomes per kilogram, reduced Saudwan mRNA up to 80% of the spinal cord motor neurons in non-human primates.

Speaker Change: Turning to slide seven.

Speaker Change: In addition to our programs targeting Tau. We're also advancing three gene therapy programs for which we expect IV filings next year.

Speaker Change: Include the wide 90, 323 wholly owned sidewall solvency program targeted with genetic cause of software that allows the neurocrine partnered for tax and gene replacement program targeting the genetic cause of friedrichs ataxia.

Speaker Change: Neurocrine partnered GBA.

Speaker Change: Gene replacement program for Parkinson's disease, and other GBM, one media diseases.

Speaker Change: As a reminder, we have demonstrated that a single IV administration of <unk> $93 23 at a clinically relevant dose of <unk> vector genomes per kilogram reduced starwood mrna up to 80% in the spinal cord motor neurons in non human primates, we expect to file an IND for <unk> 90, 323 in the middle of next.

Toby Ferguson: We expect to file an eye-and-e for VY 93-23 in the middle of next year, and initiate clinical trial in Saudwan aileist patients after the eye-and-e is accepted. Consistent with our strategy to generate rapid proof of biology in our clinical programs, we aim to assess validated biomarkers of target engagement and disease progression in this trial, including measuring levels of Saudwan in the cerebral spinal fluid and levels of neurofilament in the plasma. Importantly, since this program has the potential to generate the first clinical data for gene therapy employing a tracer capsid, we believe it could further de-risk our broader CVS gene therapy pipeline.

Speaker Change: Year.

Speaker Change: And initiate clinical trial and Starwood aerospace's after the IND is accepted.

Speaker Change: Consistent with our strategy to generate rapid proof of biology, and our clinical programs. We aim to assess validated biomarkers of target engagement and disease progression in this trial, including measuring levels of sod one in the cerebral spinal fluid.

Nate: Of north filament in the plasma importantly, since this program has the potential to generate the first clinical data for gene therapy employee a tracer capsid, we believe it could further derisked, our broader CNS gene therapy pipeline with that I'll turn the call over to Nate.

Nathan Jorgensen: With that, I'll throw the call over to Nate. Thanks, Toby. I just want to say that I'm grateful to be here today and to be a member of the Voyager team. Given my background in neuroscience and my experience on the buy side, the cell side, and as a public company CFO, I am deeply familiar with the tremendous value remaining to be unlocked in treating CNS diseases, as well as the risks. One of the reasons that I joined Voyager was that I appreciated the way the company is working to systematically reduce risk across this pipeline and thereby increase the probability that its potentially transformative programs will succeed in the clinic.

Nathan Jorgensen: I just want to say that I'm grateful to be here today and to be a member of the Voyager team. Given my background in neuroscience and my experience on the buy side, the sell side, and as a public company CFO, I am deeply familiar with the tremendous value remaining to be unlocked in treating CNS disease, as well as RISC. One of the reasons that I joined Voyager was that I appreciated the way the company is working to systematically reduce risk across this pipeline and thereby increase the probability that its potentially transformative programs will succeed in the clinic. On slide eight, I have outlined what I see as four compelling elements of this de-risking strategy. Number one, reducing risk at the target level by focusing on targets validated by human genetics.

Nate: Thanks Tobey.

Nate: I just wanted to say that I'm grateful to be here today and to be a member of the Voyager team.

Nate: Given my background in neuroscience and my experience on the buy side sell side and as a public company CFO I am deeply familiar with the tremendous value remaining to be unlocked in treating CNS diseases as.

Nate: As well as the risks.

Nate: One of the reasons that I joined Voyager was that I appreciated the way the company is working to systematically reduce risk across this pipeline and thereby increase the probability to that is potentially transformative programs will succeed in the clinic.

Nathan Jorgensen: On slide eight, I have outlined what I see as four compelling elements of this de-risking strategy. Number one, reducing risk at the target level by focusing on targets validated by human genetics. Number two, reducing risk at the delivery level by pioneering an industry-leading platform aimed to overcome delivery hurdles posed by the blood-brain barrier. And three, reducing risk at the clinical development level by focusing on disease areas and biomarkers that enable an efficient path to clinical proof of biology and value creation. And one, dear to my heart, reducing risk at the financial level by selectively partnering programs to share risk, create near term value, and reduce internal R&D spend while maintaining substantial upside.

Nate: On slide eight I have outlined what I see ads for compelling elements of this de risking strategy.

Nate: Number one reducing risks at the target level.

Nate: By focusing on targets validated by human genetics number two reducing risk.

Nate: The delivery level by pioneering an industry, leading platform aimed to overcome delivery hurdles posed by the blood brain barrier and.

Nathan Jorgensen: Reducing risk at the clinical development level by focusing on disease areas and biomarkers that enable an efficient path to clinical proof-of-biology and value creation, and one dear to my heart, reducing risk at the financial level by selectively partnering programs to share risk, create near-term value, and reduce internal R&D spend while maintaining substantial uptake, given the high unmet need in the neurospace and Voyager's unparalleled team of experts in I believe Voyager is uniquely positioned to overcome fundamental challenges in neurology and create tremendous value for both patients and shareholders. I look forward to connecting with many of you at upcoming investor conferences and events, and please do not hesitate to reach out with any questions. With that, I'll pass it back over to him.

Nate: Three.

Nate: <unk> seen risk at the clinical development level by focusing on disease areas and biomarkers that enable an efficient path to clinical proof of biology biology and value creation.

Nate: And one dear to my heart, reducing risks at the financial level.

Nate: By selectively partnering programs to share risk create near term value and reduce internal R&D spend while maintaining substantial upside.

Nathan Jorgensen: Given the high onment need in the narrow space and Voyager's unparalleled team of experts in neuroscience drug development, I believe Voyager is uniquely positioned to overcome fundamental challenges in neurology and create tremendous value for both patients and share. Holders.

Nate: Given the high unmet need and in aerospace in Voyager's unparalleled team of experts in neuroscience drug development.

Nate: I believe Voyager is uniquely positioned to overcome fundamental challenges in neurology and create tremendous value for both patients and shareholders.

Nathan Jorgensen: I look forward to connecting with many of you at upcoming investor conferences and events, and please do not hesitate to reach out with any questions.

Nate: I look forward to connecting with many of you at upcoming Investor conferences and events and please do not hesitate to reach out with any questions.

Alfandrak: With that, I'll pass it back over to Al. Thanks, Nate. As you can see on slide nine, Voyager continues to deliver on expectations for 2024. We have advanced our pipeline, our platform and our partnerships, as well as executed at 100 million dollar public offering and strengthened our leadership team.

Al Sandrock: With that I'll pass it back over to al.

Al Sandrock: Thanks Nate.

Alfred Sandrock: As you can see on slide 9, Voyager continues to deliver on expectations for 2024. We have advanced our pipeline, our platform, and our partnerships, as well as executed a $100 million public offering and strengthened our leadership team, with a robust slate of clinical milestones expected in the next 12 to 24 months. A maturing partnership portfolio with top-tier collaborators and a cash runway into 2027. We believe Voyager is poised to drive significant value creation over both the near and long term. Finally, I'd like to thank all of our employees for their hard work and dedication to improving the lives of patients. With that, we will open the call to questions. Operator.

Speaker Change: As you can see on slide nine Voyager continues to deliver on expectations for 2024.

Speaker Change: Advanced our pipeline, our platform and our partnerships as well as executed a $100 million public offering and strengthen our leadership team.

Alfandrak: With a robust slate of clinical milestones expected in the next 12 to 24 months, a maturing partnership portfolio with top tier collaborators, and cash runway into 2027, we believe Voyager is poised to drive significant value creation over both the near and long term.

Speaker Change: With a robust slate of clinical milestones expected in the next 12 to 24 months.

Speaker Change: A maturing partnership portfolio with top tier collaborators and cash runway into 2027, we believe Voyager is poised to drive significant value creation over both the near and long term.

Alfandrak: Finally, I'd like to thank all of our employees for their hard work and dedication to improving the lives of patients.

Speaker Change: Finally, I'd like to thank all of our employees for their hard work and dedication to improving the lives of patients.

Unknown Executive: With that, we will open the call for questions, Operator. Thank you. At this time, we will conduct the question-and-answer session. As a reminder, to ask the question, you will need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster.

Speaker Change: With that we will open the call for questions operator.

Operator: Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you will need to press star one on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. The first question comes from Jack Allen on behalf of Baird. Go ahead. Your line is open.

Speaker Change: Thank you at this time, we will conduct a question and answer session.

Speaker Change: As a reminder.

Speaker Change: Asked a question you will need to press star one on your telephone and wait for your name to be announced.

Speaker Change: So let's draw your question. Please press star one again.

Speaker Change: Please standby, while we compile the Q&A roster.

Jack Allen: First question comes from Jack Allen with Baird. Go ahead. Your line is open. Great. Thank you so much for taking the question and for all of the updates. Congratulations on the progress made over the course of the quarter. I apologize. Is coming in and out.

Speaker Change: First question comes from Jack Allen with Baird Go ahead. Your line is open.

Jack Allen: Great. Thank you so much for taking the question and for all the updates. Congratulations on the progress made over the course of the quarter. I apologize for coming in and out as I actually lost power where I am here in Ohio.

Jack Allen: Great. Thank you so much for taking the question.

Speaker Change: Charles Congratulations on the progress made over the course of the quarter I apologize thats coming in and out if I had actually lost power of Hawaiian here in Ohio.

Jack Allen: I actually lost power over where I am here in Ohio, but I wanted to ask about the cadence of the three gene therapy programs that are expected to enter the clinic in 2025. Do you have a sense for which of those programs made me more advanced as compared to others? And then, as it relates to the internal sauce, one ALS program, how could we look at impacts on biomarkers there? I think it was a matter of weeks or months as it relates to the ASO's impact. I'd love to hear your thoughts as it relates to how could we see early indications of effects from that gene therapy that's internally owned.

Jack Allen: But I wanted to ask about the timeline for the three gene therapy programs that are expected to enter the clinic in 2025. Do you have a sense for which of those programs may be more advanced as compared to others? And then, as it relates to the internal SOTS 1 ALS program, how quickly can we look at impacts on biomarkers there? I think it was a matter of weeks or months as it relates to the ASOs impact. I'd love to hear your thoughts as it relates to that.

Speaker Change: Wanted to ask about the cadence of the three gene therapy programs that are expected to enter the clinic in 2025 do you have a sense for which of those programs may be more advanced as compared to others and then as it relates to the internal thoughts on AOS program. How quickly can we look at impacts on Biomarkers. There I think it was a matter of weeks or months as it relates to the <unk> impact I'd love to.

Speaker Change: Here your thoughts as it relates to how quickly we could see early.

Alfandrak: Thanks, Jack.

Alfred Sandrock: Thanks, Jack. This is Al.

Alfandrak: This is Al.

Toby Ferguson: I'll start, and then I'll ask Toby to answer the second question. So, in terms of the cadence, you know, I mean, the one thing that we are in control of is our wholly owned SOD1 gene therapy program. And, you know, we expect to file an I&D roughly the mid 20, 25 prime frame, and hopefully, you know, we'll get sailed through the FDA process and we can start shortly thereafter in clinical trials. In terms of the other programs, those are partner programs. We know from our partners that they expect to file I&Ds in 2025 as well, but other than that, I'm not certain I can say more about the cadence.

Alfred Sandrock: I'll start and then I'll ask Toby to answer the second question. So, in terms of the cadence, you know, I mean, the one thing that we are in control of is our wholly owned SOD1 gene therapy program. And, you know, we expect to file an IND roughly in the mid-2025 timeframe. And hopefully, we'll get sailed through the FDA process, and we can start clinical trials shortly thereafter. In terms of the other programs, those are partner programs. We know from our partners that they expect to file INDs.

Toby Ferguson: Toby? Jack, thanks for the question. I think you've got the idea right.

Toby Ferguson: Toby.

Toby Ferguson: Jack, thanks for the question. I think you've got the idea correct. I think fundamentally, the the person program has taught us that you can see you can observe with effective sod reduction, a change in neurofilament. And also you can measure target engagement by measuring CSS SOD1 to remind that the Biogen program saw about a 40% reduction of CSS SOD1. And that's the first part of marker we would be looking at.

Toby Ferguson: I think fundamentally the Tuferson program has taught us that you can observe with effective SOD reduction a change in neurofilament, and also you can measure target engagement by measuring CSF SOD 1. To remind you, the Biogen program saw about a 40% reduction in CSF SOD 1, and that's the first biomarker we would be looking at. Of course, we'll also be looking at neurofilament to understand the changes observed there.

Speaker Change: In mind.

Speaker Change: Biogen program saw about a 40% reduction of CSF sub one and Thats. The first biomarker, we would be looking at and of course, we'll also be looking at north <unk> to understand the changes observed there.

Toby Ferguson: Of course, we'll also be looking at neurofilament understand the changes observed there.

Toby Ferguson: Great, thank you so much for that response. Maybe just Toby really briefly, how quickly was that effect on sort of one in neurofirm and light chain scene in the Biogen study? I'm trying to get a sense for how quickly we could see early indications of efficacy. So fundamentally, remember Biogen is an interesting, particularly administer ASO. There's neurofilment changes. Started to be observed by eight weeks; by 12 to 16 weeks, they'd reached their native. I think the point to make here is, though this is an ASO.

Toby Ferguson: Great, thank you so much for that response. Maybe just, Toby, really briefly, how quickly was that effect on SOD1 and neurofeminin light chain seen in the Biogen study? I'm trying to get a sense for how quickly we could see early indications of efficacy.

Speaker Change: Great. Thank you so much for that response, maybe just Toby really briefly how quickly was that effect on sod one in there from mid light chain scene in the Biogen I'm trying to get a sense for how quickly we could see early indications of efficacy.

Toby Ferguson: So fundamentally, Remember that Biogen is an intrathecally-administered ASO. Those neurofilament changes started to be observed by eight weeks. By 12 to 16 weeks, they had reached their nadir. I think the point to make here is that this is an ASO. We, of course, are administering gene therapy, and so those timelines may be different, and we need to work through that.

Speaker Change: So fundamentally.

Speaker Change: Remember biogen's into interesting, particularly administered ASO does north film on changes.

Speaker Change: Started to be absorbed by eight weeks by.

Speaker Change: By 12 to 16 weeks they had reached their nadir I think the point to make here is though this is an ASO. We of course are administering gene therapy. So those time lines may be different and we need to work through that and what about the <unk>, one and <unk> I think that can be seen as early as <unk>.

Toby Ferguson: We, of course, are administering gene therapy, and so those timelines may be different and only need to work through that. You want about the SOD-1? And SOD-1, I think that can be seen as early as starting to be seen in four weeks, but really 12 weeks is really when you start to see an effect for SOD-1.

Toby Ferguson: And what about the SOD-1? The SOD-1, I think...

Toby Ferguson: And SOV-1, I think that can be seen as early as... starting to be seen in four weeks, but really, 12 weeks is really when you start to see an effect for us.

Speaker Change: You're starting to be seen at four weeks, but really 12 weeks is really when you start to see an effect for SD Wan.

Jack Allen: Great, thank you so much.

Jack Allen: Great, thank you so much, and congratulations on the progress. I'll jump back into the queue. One moment.

Speaker Change: Got it great. Thank you so much and congratulations on progress I'll jump back in the queue.

Unknown Executive: Thank you for that.

Unknown Executive: There's no progress.

Unknown Executive: I'll jump back in the queue. One moment for our next question.

Operator: One moment for our next question. The next question comes from Divya Rao with T.D. Cohen. Go ahead. Your line is open.

Speaker Change: One moment for our next question.

Speaker Change: Okay.

Speaker Change: Yeah.

Vivia Rout: The next question comes from Vivia Rout with TV Cohen. So ahead, your line is open. Hi guys, this is Vivia on for Phil. I have two questions. One for DUI 7523. Could you give us an idea of how many of those levels you're exploring? And then, based on the preclinical models that you have so far, how many doses do you think you need to step through to hit what would be considered an active dose when I have a follow-up question? Thank you for the question.

Speaker Change: The next question comes from Dave Your route with TD Cowen Go ahead. Your line is open.

Divya Rao: Hi, guys. This is Divya speaking on behalf of Phil. I have two questions. One is about DY7523. Could you give us an idea of how many dose levels you're exploring? And then, based on the preclinical models that you have so far, how many doses do you think you need to step through to hit what would be considered an active dose? And then there's a follow-up question.

Speaker Change: Hi, guys. This is davita entre count.

Speaker Change: I have two questions one for D Y seven by Q3.

Toby Ferguson: Thank you for the question; this is Toby. Fundamentally, to remind you of single ascending doses and healthy volunteers, we're looking at multiple doses. We haven't disclosed the dose, but frankly, based on the preclinical models that measure tau spread, we think we understand the exposures we need to get tau spread. And based on the SAT data, we will understand those exposures and move forward with a MAT study next year. Todd, do you want to answer the question?

Toby Ferguson: This is Toby. To remind you, the single ascending doses in healthy volunteers; we're looking at multiple doses. We haven't disclosed those, but frankly, we think based on the preclinical models that measure Towspread. We think we understand the exposures we need to get Towspread. And based on the sad data, we will understand those exposures and move forward with a math study next year. So how do you want to answer the second part? So the second part of the question being what are the doses that we expect to be able to achieve something relative to our preclinical models?

Todd Carter: Todd, do you want to answer the second part?

Todd Carter: So the second part of the question is, what are the doses that we expect to be able to achieve something relative to our preclinical models? What we've done is, we're basing it off of the modeling for the PK studies, and we know that we're able to achieve approximately 70% or better knockdown or reduction of tau pathology in the seeding model that Toby referred to. So what we're doing is aiming to achieve the level of exposure of our antibody in the brain and the CNS of patients to that level that we need to achieve that 70% knockdown. And so our dosing is based on that correlation. Of course, the data that we get from the PK in the studies will really dictate when we achieve that.

Toby Ferguson: What we've done is we're facing it off of the modeling for the PK studies. And we know that we're able to achieve approximately 70% or better knockdown or reduction of taupe methodology in the seeding model, that's totally referred to. So what we're doing is we're aiming to achieve the level of exposure of our antibody in the brain in the CNS of patients to that level that we needed to achieve that 70% knockdown. So our goal thing is based on that correlation; of course, the data that we get from the PTA in the studies will really dictate when we achieve that.

Vivia Rout: Guy, that's helpful.

Divya Rao: Thanks guys, that's helpful. And then my second question is just, so there are two kinds of programs that you're looking at going after tau specifically in patients with Alzheimer's. Should we think of those programs both kind of going after the same population, or do you think that the vectorized, or sorry, the tau silencing gene therapy lends itself to a specific subpopulation? Thank you.

Toby Ferguson: And then my second question is just, so there's two kind of programs that you're looking at going after Tows, specifically in patients with Alzheimer's. So we think of those programs both kind of going after the same population, or do you think that they're vectorized, or sorry, the Tows, balancing gene therapy lend itself to a specific population? Thank you. I think fundamentally I'd say that. One, the talent body program is ahead, and there remains a strong unmet need in patients with Alzheimer's disease. I think we've seen from the beta amyloid data that can be used to be disease progression.

Speaker Change: So I don't see in gene therapy lends itself to a specific sub population. Thank you.

Toby Ferguson: I think fundamentally, I'd say that One, the Italian body program is ahead, and there remains a strong unmet need in patients with Alzheimer's disease. I think we've seen from the beta amyloid data that there continues to be disease progression. I think first and foremost that we think Tau is an incredibly important target in and of itself. And we'd be incredibly excited to advance an antibody and an ASO that knocks down Alt-Tau. So I think that's sort of the most straightforward point I would make. Yeah, maybe I could add that.

Speaker Change: I think fundamentally I would say that.

Speaker Change: One the Italian Lottery program is ahead and there remains a strong unmet need in patients with Alzheimer's disease, I think we've seen from our beta amyloid data there continues to be disease progression.

Toby Ferguson: So the first and foremost, we think Tau is an incredibly important target in and of itself. And we've been incredibly excited to advance antibody and ASO that knocks down all tau. So I think that's sort of the most straightforward one I would make. Yeah, maybe I could add that in the case of the spreading, you know, the antibody is meant to block the spread of pathological tau. So we would want to choose patients where the spread has just started, essentially, and then choose an area of the brain to measure the spread too. And so in the staging, it would be stage two or stage three patients likely.

Speaker Change: First and foremost we think.

Speaker Change: Tau is an incredibly important targeted in of itself.

Speaker Change: We are incredibly excited to advance <unk> antibody and a so that knocks down wholesale so I think that's sort of the most.

Speaker Change: Both straightforward point I would make.

Toby Ferguson: Yeah, maybe I could add that in the case of the spreading, you know, the antibody is meant to block the spread of pathological tau. So we would want to choose patients where the spread has just started, essentially, and then choose an area of the brain to measure the spread to. And so in the staging, it would likely be stage two or stage three patients. In case of a knockdown, we're gonna be able to follow what, you know, we're gonna be tracking the VIV-80 program, right? And that's a knockdown approach using an ASO. So there, we're gonna learn a lot from that. And I suspect we'll model our study after that, including the stage of patients.

Speaker Change: Yes, maybe I could add.

Speaker Change: In the case of the spreading the antibody is meant to block the spread of pathological tower. So we would want to choose patients where the spread is just started essentially.

Speaker Change: And then choose an area of the brain to measure.

Speaker Change: Read too.

Speaker Change: And so.

Speaker Change: In the staging it would be stage, two or stage three patients likely.

Toby Ferguson: In the case of the knockdown, we're going to be able to follow what, you know, we're going to be tracking the 580 program, right? And that's a knockdown approach using an ASO. So, there, we're going to learn a lot from that. And I suspect we'll model our study after that, including the stage of patients. Thank you.

Speaker Change: The case of the knockdown, we're going to be able to follow.

Speaker Change: We're going to be tracking the bid of 80 program right.

Speaker Change: That's a knockdown approach using an ASO. So there we're going to learn a lot from that and I suspect well.

Speaker Change: Model, our study after that including the stage of patients.

Ry Forset: One moment for our next question. Our next question comes from Rye Forset with Guggenheim Securities. Go ahead. Your line is open.

Operator: One moment for our next question. Our next question comes from Ry Forseth with Guggenheim Securities. Go ahead, your line is open.

Alfandrak: Hey, this is Rye from Deadgit's team. Did you discuss the potential of the tracer platform to yield capsids with multi-organ and specifically potentially fit for addressing indications, such as DM1, where there's both central and neuromuscular pathology?

Alfandrak: Well, I'll start and I'll finish. Yeah, in some ways it applies not just to DM1, but also to Friedrich Ataxia, which involves a nervous system in the heart. You know, the way we look at it is that the tracer that finds looks for variations in the capsid that give an endowed the capsid with an additional tropic activity. So in our hands, since AV9 works pretty well for cardiac muscle on its own, you don't have to necessarily enhance that. And if the tracer derived capsid gets the additional property of also getting into the brain, but retains its property of that's using heart muscle, then that's that that would be an ideal capsid. I bring up the heart, by the way, because DM1 also affects the heart.

Unknown Executive: Well, that's a I'll start and finish. Yeah, in some ways, it applies not just to DM1, but also Friedreich's ataxia, which involves the nervous system in the heart. You know, the way we look at it is that the tracer, the finder, looks for variations in the capsid that endows the capsid with an additional trophic activity. So, in our hands, since AAV9 works pretty well for cardiac muscle on its own, you don't necessarily have to enhance it.

Unknown Executive: And if the tracer-derived capsid gets the additional property of also getting into the brain but retains its property of transducing heart muscle, then that would be an ideal capsid. And I bring up the heart, by the way, because DM1 also affects the heart. In terms of skeletal muscle, we do look at skeletal muscle transduction, and we will choose capsids that obviously can do that.

Todd Carter: In terms of skeletal muscle, you know, there we do look at skeletal muscle transduction, and we will choose capsids that obviously can do that.

Speaker Change: Total muscle transduction and.

Speaker Change: And we will choose capsid that obviously can do that.

Todd Carter: We haven't said that we have at the end one program, by the way, but that's why I started with Friedrich Ataxia. But Todd, do you want to.

Todd: But we haven't said that we have at the <unk> program by the way, but that's why I started with the <unk> ataxia, but Todd you want to.

Unknown Executive: Sure. So we do look at quite a wide variety of tissues throughout the non-human primates when we're identifying and selecting our capsids. In fact, for any given disease, we actually build a capsid profile, a target capsid profile. Different diseases, different CNS diseases, at different relative delivery.

Todd Carter: Sure, so we do look at quite a wide variety of tissues throughout the throughout the non human primates. When we're identifying and selecting our capsids, in fact, for any given disease, we actually go to the capsid profile, tardy capsid profile, different diseases, different CNS diseases. have different relative delivery needs to even different parts of the brain. We also look for deep targeting for off-target tissues like the liver. And so we do evaluate quite a number of tissues, and what we are seeing is that we have different kinds of capsic profiles that are coming out of our capsic screens.

Speaker Change: Sure.

Todd: We do look at quite a light variety of tissue throughout the.

Todd: Throughout the nonhuman primates.

Todd: When we're identifying and selecting a capsid and in fact for any given disease, we actually build a capsid profile target capsid profile.

Todd: Different diseases different CNS diseases.

Speaker Change: Have different relative delivery needs.

Unknown Executive: Needs to even target different parts of the brain. We also look for deep targeting for off-target tissues like the liver. And so we do evaluate quite a number of tissues, and what we are seeing is that we have different kinds of capsid profiles that are coming out of our capsid screens. So what that results in are different capsid families that have different potentials and opportunities for being deployed for different diseases. And that includes greater or lesser delivery to places like the muscle, the heart, various brain regions, and, of course, those off targets. So I think the answer is that we do see the opportunity for TRACER to deliver opportunities for not just the CNS but for other diseases as well.

Speaker Change: Needs to even different parts of the brain.

Todd: We also look for D targeting for off target tissues like liver.

Speaker Change: So we do evaluate quite a number of tissues and what we're seeing is that we have different kinds of captured profiles that are coming out of our catch it screens. So that results in our different tests and families that have different.

Todd Carter: So with that results in our different types of families that have different potentials and opportunities for being deployed for different diseases. And that includes greater or lesser delivery to places like the muscle, the heart, various brain regions, and of course those off targets. So I think the answer is we do see the opportunity for Tracer to deliver opportunities for not just the CNS but in other diseases as well.

Speaker Change: Okay.

Speaker Change: Potentials and opportunities for being deployed for different diseases, and that includes greater or lesser delivery to places like the muscle of the heart various brain regions and of course was off targets. So I think the answer is we do see the opportunity for tracer to deliver opportunities.

Speaker Change: We're not just the CNS, but in other diseases as well.

Unknown Executive: Thank you.

Speaker Change: Thank you.

Speaker Change: One moment for our next question.

David: Next question comes from David with City Group. Go ahead; your line is open.

Operator: One moment for our next question. The next question comes from David with Citigroup. Go ahead. Your line is open.

Unknown Executive: Hi, this is Sean on Dave's team from Citi. Thank you for taking our questions.

David: Yeah, hi, this is Sean on this team from City. Thank you for taking our questions. I guess one question that we had is, can you speak to the potential competitive position of your NPTEL therapies versus Biogen's program?

Toby Ferguson: And second question, let's do the facility one, some of which is therapy. I'm just curious what are some of the remaining getting factors to get to the eye of defining. Thank you.

Alfandrak: Well, I'll answer the first question on Tau, and then maybe Toby could answer the second question on SOB1. So, on terms of Biogen, they have a big 80 program. They did have an anti-tau program directed against the N-terminal, as Toby mentioned. That that that antibody was terminated after and not producing the results that were acceptable. And so and so there are, however, a number of other companies pursuing anti-tau antibodies, at least four other companies that we know of targeting various different different epitopes. None are against directed against the N-terminal, probably because everybody thinks that the N-terminal is not a great epitope. But some are targeting the mid-domain, some are targeting the MTBR, and some ends, and like us, one of the companies targeting the C-terminal.

Unknown Executive: Well, I'll, I'll answer the first question on TAO. And then maybe Toby could answer the second question on it.

Alfred Sandrock: So do you want to, you know, in terms of Biogen, they have a BIB 80 program, they did have an NT Tau program directed against the end terminal, as Toby mentioned, that antibody was terminated after not producing the results that were acceptable. And so there are, however, a number of other companies pursuing anti-tau antibodies, at least four other companies that we know of targeting various different different epitopes. None are directed against the N-terminal, probably because everybody thinks that the N-terminal is not a great epitope, but some are targeting the mid-domain, some are targeting the MTBR, and, like us, one of the companies targeting the C-terminal. Fundamentally, the vectorized siRNA approach is, you know, as Toby indicated, we're not in the clinic yet. We do expect to file an IND in 2026.

Alfandrak: Fundamentally, the vectorized SIRNA approach is, you know, as Toby indicated, we're not in the clinic yet. We do expect the file on IND in 2026. But you know, so we're way behind that; if you will, the B-80 program, which is already in the clinic and starting to produce some interesting results. I would just add that in concept, it's very similar in the sense that it's knocking down the expression of all forms of Tau, about intracellular and extracellular. So it's decreasing the expression of Tau, essentially, in the nervous system. So, in that sense, it produces, we think, a relatively equivalent effect on Tau.

Alfred Sandrock: But, you know, so we're way behind, if you will, the BIB 80 program, which is already in the clinic and starting to produce some interesting results. I would just add that, in concept, it's very similar in the sense that it's knocking down the expression of all forms of tau, both intracellular and extracellular. So it's decreasing the expression of tau, essentially, in the nervous system. So in that sense, it produces, we think, a relatively equivalent effect on tau. Toby, do you want to take the second question? Sure, maybe I'd add one other point of emphasis on top.

Speaker Change: Expression of Tau essentially.

Speaker Change: In the nervous system, so in that sense.

Speaker Change: It produces we think are relatively equivalent.

Speaker Change: Effect on Tao.

Toby Ferguson: Toby, do you want to take the second question?

Speaker Change: There'll be do you want to take the second question, Joe maybe I'd add one other point of emphasis on the Tau program before I do just to highlight that the Pfizer program of course is in particularly administered and our program is a onetime IV administrated program sort of in keeping with our strategy of.

Toby Ferguson: Sure, maybe I'd add one other point of emphasis on the TAL program before I do. Just to highlight that the Voyager program, of course, is intrathecally administered, and our program is a one-time IV-administrated program, sort of in keeping with our strategy of I'm pursuing with our novel tracer capsids relatively de-risked harvest. On the SOD program, I think fundamentally what we've highlighted is that program; we closed that program as we started the toxicology programs, and that's the main key next step for moving the program forward for the ice.

Toby Ferguson: Sure, maybe I'd add one other point of emphasis on the Tau problem before I do.

Toby Ferguson: Just to highlight that the body of program, of course, is a particularly administered, and our program is a one-time IV administrative program, sort of in keeping with our strategy of pursuing with our novel on the SOD program. Think for a member of what we've highlighted is that that program, which we've to close that program, has started to touch college programs, and that's the main key next step for moving the program forward for the I&D. Thank you.

Joe: Pursuing with our novel <unk> relatively de risked targets.

Speaker Change: On the <unk> program I think fundamentally what we've highlighted is that that program, which we've closed that program as we started the toxicology programs and Thats. The main key next step for moving the program forward for guidance.

Speaker Change: Thank you.

Jay Olson: And bye for our next question. The next question comes from Jay Olson with Oppenheimer. Go ahead; your line is open.

Operator: Standby for our next question. The next question comes from Jay Olson with Oppenheimer. Go ahead. Your line is open.

Speaker Change: And our next question.

Speaker Change: The next question comes from Jay Olson with Oppenheimer Go ahead. Your line is open.

Jay Olson: Go ahead; this is John, the line for Jay. Thanks for taking the question, and congrats on the progress. It'd be like a two-part or two-question from us. First, we're just wondering if there's like a mechanism rationale to support behind the liver detoxing of the trees or capsules and this way to further enhance the liver detoxing. And secondly, I'm just wondering for the ALPL binding, Lincoln, for new modalities, curious about any particular modality you are thinking about to prioritize. Thank you so much.

Unknown Executive: Oh, hey, this is John on the line for Jay. Thanks for taking the question and congrats on the progress. Maybe like a two part or two question from us. First, we're just wondering if there's like a mechanism rationale to um support the liver de-targeting of the tracer capsid and this way to further enhance the liver de-targeting. And secondly, I'm just wondering about the ALPL binding, looking for new modalities, and curious about any particular modality you are thinking right now about prioritizing. Thank you so much.

Speaker Change: Oh, Hey, Thanks. This is John on the line for James Thanks for taking the question and congrats on the progress you might be like a two part.

Speaker Change: Question from Alice Firstly, we're just wondering if there is like a mechanism rationale too.

Alfred Sandrock: So I'll ask Todd to answer the first question, and I'll take the second one.

Alfandrak: So I'll add a pod down to the first question, and I'll take the second one. Sure.

Todd Carter: Sure, so the first question was, effectively, mechanistically, why are capsids de-targeted from the liver? And I can answer that in two parts.

Todd Carter: So the first question was effectively mechanistically, why are capsules de-targeted from the liver? And I can answer that in two parts. One, this is something that we're seeing with a variety of our different capsid families, and others have reported this too for capsules that cross the blood-brain barrier. It's an empirical observation that many of these capsules deliver to the liver less than they deliver elsewhere, or less than the parental capsules do for those that don't deliver across the blood-brain barrier. As to the reasons why we can speculate, some of it is, you know, that subtle changes that affect the charge of the capsid can impact things like liver delivery.

Todd Carter: One, this is something that we're seeing with a variety of our different capsid families, and others have reported this, too, for capsids that cross the blood-brain barrier. It's an empirical observation that many of these capsids deliver to the liver less than they deliver elsewhere, or less than the parental capsids do for those that don't deliver across the blood-brain barrier. As to the reasons why, we can speculate. Some of it is because we know that subtle changes that affect the charge of the capsid can impact things like liver delivery.

Todd Carter: The other is, again, with relating to the empirical observations, is that we are choosing to move forward those capsids that are de-targeted from the liver. This is part of our selection criteria and something that we're specifically looking for to reduce the potential for an AELT off-targeted problems. So, and just a quick answer to the second question on ALPL. So you're correct. We are interested in using ALPL binding ligands and conjugating various macro molecules to them to see if we can get them across the BBB. And, you know, we're testing proteins such as therapeutic antibodies and enzymes.

Todd Carter: The other is, again, relating to the empirical observations, is that we are choosing to move forward those capsids that are already targeted from the liver. This is part of our selection criteria and something that, Transcripts provided by Transcription Outsourcing, LLC. And just a quick answer.

Unknown Executive: We are interested in using ALPL binding ligands and conjugating various macromolecules to them to see if we can get them across the BBB. And, you know, we're testing proteins. Such as therapeutic antibodies and enzymes. We're also going to be looking at whether or not they can transport oligonucleotides, both ASOs and siRNAs. And, yeah, we're doing those experiments now.

Unknown Executive: And just a quick answer to the second question on ALPL. So, you're correct.

Todd Carter: We're also going to be looking at whether or not they can transport all of your nucleotides, both ASOs and siRNAs. And, yeah, we're doing those experiments now. Thank you.

Operator: One moment for our next question. The next question comes from Yoon Lee with Truist. Go ahead. Your line is open.

Yana: Next question comes from Yunli with Truist. Go ahead. Your line is open. Hi. Good afternoon. This is Median for June Concours on the progress and thanks for taking our question. So, maybe a big picture question for us.

Unknown Executive: Hi, good afternoon. This is Mahdi from the June Congress on the Progress, and thanks for taking our question. So maybe a big picture question for us. Given time to data, especially in relation to the tracer platform, and also recent advances in the field, basically on decorated AAVs, how do you see the future of CNS-targeted AAVs in the next 12 to 18 months? And also, how do you plan to ensure your leadership position in this space? Thank you.

Yana: Given time to data, especially in relation to Placer platform, and also recent advances in the field, basically, on decorated AABs, how do you see the future of CNS targeted AABs in the next 12 to 18 months, and also how you plan to ensure your leadership position in this space? Thank you. Oh, thank you. That's an interesting question. And, you know, look, we have to be aware of the fact that there are multiple other companies pursuing the approach that, you know, that I believe the Voyager scientists pioneered and not just modifying the AAB, but, as you just pointed out, decorating, if you will, AAB with, for example, TFR binding motifs.

Speaker Change: Your next 12 to 18 months.

Speaker Change: And also how you plan to ensure your leadership position in this space.

Alfred Sandrock: Oh, thank you. That's a, that's an interesting question. And, you know, look, we have to be aware of the fact that there are multiple other companies pursuing the approach that, you know, that I believe the Voyager scientists pioneered, and not just modifying the AAV but, as you just pointed out, decorating, if you will, AAV with, for example, TFR binding motifs. And, and so those are all viable. Approaches, potentially, but we don't know until we do the experiments in humans which ones will work. I would say that in the future, what we're going to see is.

Speaker Change: Thank you that's a it's an interesting question and look we have to be aware of the fact that there are multiple other companies predict pursuing the approach that.

Speaker Change: I believe the Voyager scientists pioneered.

Speaker Change: Not just modifying the AAV, but as you just pointed out decorating if you will AAV with for example.

Speaker Change: TFR binding motifs.

Alfandrak: And so those, those are all viable approaches, potentially, but we don't know until we do experiments in humans, which ones will work.

Speaker Change: And and so those those are all viable approaches potentially but we don't know until we do the experiments in humans, which ones will work I would say that in the future of what we're going to see us.

Alfandrak: I would say that in the future, what we're going to see is, for example, the earlier question, what other tissues can you target besides the brain? Because several diseases involved more than just the CNS. Second is cell type tropism. So it's not just the tissue; we want to target certain cells. And sometimes it's neuron, sometimes it's glial cells, sometimes it's all like a dendrocyte, sometimes it's a combination of those cell types. And, and then there's the D targeting, not only the deliver, but also other potential cells of toxicity, such as Dorsaroo ganglion neurons. So when you add all that together, I think there's going to be a need for multiple capsids that are going to be required for certain diseases.

Alfred Sandrock: For example, the earlier question, what other tissues can you target besides the brain? Because several diseases involve more than just the CNS. Second is cell type tropism. So, it's not just the tissue; we want to target certain cells. And sometimes it's neurons, sometimes it's glial cells, sometimes it's oligodendrocytes, sometimes it's a combination of those cell types. And then there's the de-targeting, not only of the liver but also of other potential cells of toxicity, such as dorsal root ganglion neurons. So, when you add all that together,

Speaker Change: For example, the earlier question what other tissues.

Speaker Change: Can you target besides the brain because several diseases involved more than just the CNS second is cell type tropism. So it's.

Speaker Change: It's not just the tissue, we want to target certain cells and sometimes it's neuron, sometimes it's glial cells, sometimes it's oligodendrocyte, sometimes it's a combination of those cell types.

Alfred Sandrock: It's I think there's going to be a need for multiple capsids that are, that are going to be required for certain diseases. And that's why, as Todd said earlier, we develop CAHPSID profiles for each of the diseases we're considering, and we have a pretty high bar. Finally, I'd also say that there are other issues that we should remember. Manufacturability, for example, and that's built into our development candidate criteria. There is immunogenicity, and there are potentially ways of affecting immunogenicity by making variations in the CAHPSID.

Alfandrak: And that's why, as Todd said earlier, we develop capsid profiles for each of the diseases we're considering, and we have a pretty high bar.

Alfandrak: Finally, at all, I'd also say that there's other issues that we should remember: manufacture ability, for example, and that's built into our development candidate criteria. There's immunogenicity, and there are potentially ways of affecting immunogenicity by making variations in the capsid. And so I think there's still a lot of innovation to be had, but I also want to emphasize the fact that we may want to tailor the capsids to the disease that we need to treat and the cells in which we need to get the transduction to occur in. Thank you.

Alfred Sandrock: And so I think there's still a lot of innovation to be had, but I also want to emphasize the fact that we may want to tailor the CAHPSIDs to the disease that we need to treat and the cells in which we need to get the transduction to occur in.

Operator: One moment for our next question. The next question comes from the line of Sumant Kulkarni with Conocor Genuity. Please go ahead, your line.

Unknown Executive: The next question comes from the line of Simone Cucarni with conical originality. Please go ahead. Your line is open. Thanks for taking our question. So on your anti towel programs conceptually, what are the pros and cons of targeting extracellular versus the intracellular towel? And with your gene therapy program, are you aware of any downsides of potentially one-and-done towel silencing approaches, given the role of towel in micro tube stabilization?

Alfandrak: Well, maybe I'll start in, and I'll ask my colleagues either Todd or Toby to add. You know, I would say that targeting extracellular towel is likely to be safer, as you're kind of implying in your question because you're not affecting all forms of towel and you're not affecting the intracellular towel in particular. But on the other hand, there are questions about efficacy, particularly given, as what Toby said, the antromanal antibodies have failed. And so there's that. And then, in terms of the knockdown. You know, we don't know, you know. First of all, pow, knockout animals are actually pretty, you know, they're viable.

Alfred Sandrock: Well, maybe I'll start and then I'll ask my colleagues, either Todd or Toby, to add. You know, I would say that targeting extracellular tau is likely to be safer, as you're kind of implying in your question, because you're not affecting all forms of tau, and you're not affecting intracellular tau in particular. So, but on the other hand, there are questions about efficacy, particularly given, as Toby said, that N-terminal antibodies have failed. And so there's that. And then in terms of the knockdown, you know, we don't know, first of all, Tau knockout animals are actually pretty, you know; they're viable. They actually are, and can reproduce.

Alfandrak: They actually are a reput can reproduce. And so, even though we think that there is a role for tau during development, certainly it doesn't seem to be there seems to be some tolerance for the loss of tau.

Alfred Sandrock: And so, even though we think that there is a role for Tau in, during development, certainly, it doesn't seem to be, there seems to be some tolerance for the loss of Tau. I'd say the other thing is that we're fortunate in the sense that BID 80 is going to enroll hundreds of patients into a well-controlled study. And we will have some idea of how safe they are, actually, over the long term because those studies were started a couple of years ago.

Alfandrak: I'd say the other thing is that we're fortunate. In the sense that Bib 80 is going to enroll hundreds of patients into a well-controlled study. And we will have some idea of the safety, actually, over the long term, because those studies were started a couple of years ago. So, so we should have long term data on the safety of knocking down the expression of tau. By the time we enter the clinic and start our journey ourselves, and then also in terms of the magnitude of knockdown too. I mean, we'll have some idea perhaps by then is how what is safe and what's not, Toby.

Alfred Sandrock: So, we should have long-term data on the safety of knocking down the expression of Tau. By the time we enter the clinic and start our journey ourselves, and then also in terms of the magnitude of knockdown, too, we'll, we'll have some idea, perhaps, by then, about how safe things are and what's, what's, what's not.

Toby Ferguson: I don't have much to add. I mean, I just think that the human data in particular, the experience of the baby, some of the genetic that are really suggested, at least as much as so far that knockout, how has been well tolerate. Of course, we'll need to see the longer term from data. And I think it's sort of the idea that you knock down supersede all forms of tau and really address tau tau with its totality is quite important. And for the antibody program, we really have targeted the path logic form of tau and, based on our spreading model, we think that that is a very reasonable thing to do given a knockdown we've seen.

Toby Ferguson: I don't have much to add. I mean, I just think that the human data, in particular, the experience of the baby, and some of the genetic data really suggest that, at least as far as I understand so far, knockdown Tau has been well-tolerated. Of course, we'll need to see the longer-term data. And I think it's sort of the idea that you, with knockdown, supersede all forms of Tau and really address Tau and its totality.

Toby Ferguson: And for the antibody program, really, we have targeted the pathologic form of Tau, and based on our spreading model, we think that is a very reasonable thing to do given the knockdown we've seen. And so I think that's important. And we think they could be essentially complementary to each other. I'll add just a little bit, although I think that the human debate...

Toby Ferguson: And so I think that that's important, but we think that could be essentially complimentary to each other.

Todd Carter: I'll add just a little bit, although I think that the human VIV-80 data will ultimately supersede anything preclinical. I will add that preclinical studies to date, in addition to what Al described with the cow knockout animals, all looked remarkably benign. And so people have looked at non-human primates as well as rodent species. We've done this internally in our mouse studies that we've talked about at conferences. Other people have reported on this.

Todd Carter: All right, just a little bit. Well, I think that the human survey data, the data will ultimately supersede anything preclinical. I will add that preclinical studies to date, in addition to what Al describes with the tau knockout animals. It has all looked remarkably benign. And so, people have looked at nonhuman primates as well as rodent species. We've done this internally in our mouth studies that we've talked about at conferences. Other people have reported on this, and so far, reduction of tau using gene therapy or gene therapy-like approaches has seen quite remarkably benign. So you never know until you do the ultimate human experiments, but today, things look pretty positive with regard to knockdown risk.

Speaker Change: In addition to what al described with the knock out animals.

Speaker Change: It's all up remarkably benign and so people have looked in nonhuman primates as well as rodent species. We've done this internally in our mouse studies that we've talked about it as conferences. Other people have reported on this and so far reduction of Tau using gene therapy or gene therapy like approaches has seen a.

Todd Carter: And so far, reduction of tau using gene therapy or gene therapy-like approaches has seemed quite remarkably benign. So you never know until you do the ultimate human experiment. But to date, things look pretty positive with regard to knockdown animals.

Speaker Change: Quite remarkably benign so but you never know till you do the ultimate human experiments.

Speaker Change: The day things look pretty positive.

Speaker Change: Regard to knockdown reps.

Unknown Executive: Thanks.

Speaker Change: Thanks.

Unknown Executive: One moment, please.

Speaker Change: One moment please.

Laura Chico: The next question comes from Yana and you with Wells Fargo Securities. Go ahead. Your line is open. Hi, thanks for taking our question.

Operator: The next question comes from Yanan Hu with Wells Fargo Securities. Go ahead. Your line is open.

Speaker Change: The next question comes from Jan and Hugh with Wells Fargo Securities Go ahead. Your line is open.

Unknown Executive: Hi, thanks for taking our question. This is Kwan Ang from YANA.

Hi, Thanks for taking our question. This is Kwan oncor Yana. So I have a quick question on the RNA program Oh, it's ironic so equipment, where you see the and HP data and you previously mentioned that there is a potential for combo strategy with on.

Laura Chico: This is Juan Ang for Yana. So I have a quick question on the SIA RNA program. How is RNA? So when may we see the NHP data? And you previously mentioned that there is a potential for combo strategy with the antibody. So, any updated thoughts on that would and would you seek the approval of antibody first, or would you synchronize the programs? Thank you.

Unknown Executive: So I have a quick question on the siRNA program, tau siRNA. So when may we see the NHP data? And you previously mentioned that there is a potential for a combo strategy with the antibody. So any updated thoughts on that? And would you seek the approval of the antibody first, or would you synchronize the programs?

Todd Carter: Thank you.

Speaker Change: On the antibody so any updated thoughts on that and would you seek the approval anti body first so would you synchronize the programs. Thank you.

Todd Carter: I'll ask Todd to answer the first part of the question, and Toby to answer the second part. For the first part of the question, we have ongoing experiments to drive toward development candidate identification. We've given no guidance on when we expect to have those data. So the guidance that we've given is that I indeed in 2026.

Toby Ferguson: I'll ask Todd to answer the first part of the question and Toby to answer the second part.

Speaker Change: So I'll ask Todd to answer the first part of the question and Tobey to answer the second part.

Todd Carter: For the first part of the question, we have ongoing experiments to drive toward development candidate identification. We've given no guidance on when we expect to have those data. The guidance that we have given is that IND in 2026.

Todd: For the first part of the question.

We have ongoing experiments to to drive toward development candidate identification, we've given no guidance on when we expect.

Tobey: To have those data the guidance that we've given is that the IND.

Speaker Change: In 2026.

Toby Ferguson: On the second part of the question, what I would say, you ask a question about synchronizing programs. I think fundamentally what's most important is the context that there remains strong and that need for people of all summer disease. And so we certainly, if we had positive data for our tele antibody program, which of course is in the lead, we would report with that program.

Toby Ferguson: On the second part of the question, what I would say, you asked a question about synchronizing programs. I think fundamentally what's most important in the context that there remains a strong need for people with Alzheimer's disease. And so we certainly, if we had positive data for our Tau antibody program, which, of course, is in the lead, we would move forward.

Toby Ferguson: Sorry, thank you for that, and a quick follow-up. So it's a hypothetical question for the antibody. So if you are able to stop all the spread of towel between the sales, would I be enough to save the early stage patients such as BRAC, stage two patients. Thank you. I think, fundamentally, it's a very reasonable question. I think we would, of course, be elated if we saw that. I think what we understand from the spread of towel based on talp at and talp pathology is that is the intent of this program. We'll have to figure it out of the clinic.

Toby Ferguson: Got it. Thank you for that. And a quick follow-up. So for the antibody, if you are able to stop all the spread of tau between cells, would that be enough to save early stage patients such as BRAC stage two patients? Thank you.

Toby Ferguson: I think fundamentally, it's a very reasonable question. I think we would, of course, be elated if we saw that. I think what we understand from the spread of tau based on tau path and tau pathology is that is the intent of this program. We'll have to figure it out in the clinic.

Unknown Executive: Yeah, thank you for all the comments.

Unknown Executive: Yeah, thank you for all the colors.

Laura Chico: The next question comes from Laura Chico with Web Host Security. Go ahead, Laura; your line is open. Thanks very much. And thanks for taking the question. Good afternoon.

Operator: The next question comes from Laura Chico with Wedbush Securities. Go ahead, Laura, your line is open.

Laura Chico: Thanks very much, and thanks for taking the question. Good afternoon.

Laura Chico: I wanted to ask you two questions related to the GBA-1 and the Frigidistaxia programs, just to mix it up a little bit here. Wondering if you could talk a little about the type of patients that you'll be seeking to identify, and essentially, there have been a few other gene therapy efforts kind of ongoing in these spaces, but wondering how you think about what's the appropriate window for therapeutic intervention, any color there, and then just one quick follow-up. Can you remind us about any potential remaining milestones that we should have on our radar for 24? Thank you.

Laura Chico: I wanted to ask on two questions related to the GBA one and the producer taxi of programs to mix it up a little bit here. I wonder if you could talk a little about the type of patients that you'll be seeking to identify. And essentially, there have been a few other things there for efforts kind of ongoing in these spaces, but wondering how you think about what's the appropriate window for therapeutic intervention. Any color there. And then just one quick follow-up.

Toby Ferguson: So I think for the pre-diagnostic programs, I'll remind you that these are part of the programs at Neurocrin, and they own the development of that program. I think if you look at the other programs that have gotten approval, such as Starclaris, they've looked at broad populations, both adult and some younger age patients. So I think fundamentally that there is a path there that's been paved, but this really sits with Narco. And then the milestones, I think, I think we just don't comment on milestones.

Unknown Executive: Can you run this about any potential remaining milestones that we should have in our radar for 24. Thank you. So I think for the product tax programs are reminded, these are part of programs in your opinion that they own the development of that program. I think if you look to the other programs that have gotten approval, such as Stachleris, they've looked at blood populations, both adult and some younger age patients. So he fundamentally that there is a path there that's been paved, but this really sits in sits with NARCAN. And then the milestones, I think, I think we just we don't comment on most of them.

Alfred Sandrock: I would just also add that on FAA. You know, it's great that the first drug ever for FAA was approved. The mechanism of action, it's an Nrf2 activator. It's I don't I think it's going to be. I think our drug would only add to the efficacy.

Unknown Executive: I would just say also add that on FA, you know, it's great that the first drug ever for FA was approved. The mechanism of action, it's an NRF2 activator. I don't; I think it's going to be. I think our drug would only add to the efficacy. And so because they're completely different mechanism of action, arses replacing protection. So, so I'll just say that.

Alfred Sandrock: And so because they're completely different mechanisms of action versus replacing for taxon. So so I'll just say that and then ask you, Laura, to ask a neurocriminologist some more specific questions. Hello again.

Unknown Executive: And then ask you to Laura to ask a NARCAN. More specific questions. Thank you, guys. I appreciate it. You're welcome.

Unknown Executive: Okay. Thank you, guys. I appreciate it.

Operator: Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect.

Unknown Executive: Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect. Thank you.